Class II MHC Self-Antigen Presentation in Human B and T Lymphocytes

Human CD4[superscript +] T cells process and present functional class II MHC-peptide complexes, but the endogenous peptide repertoire of these non-classical antigen presenting cells remains unknown. We eluted and sequenced HLA-DR-bound self-peptides presented by CD4[superscript +] T cells in order to compare the T cell-derived peptide repertoire to sequences derived from genetically identical B cells. We identified several novel epitopes derived from the T cell-specific proteome, including fragments of CD4 and IL-2. While these data confirm that T cells can present peptides derived from the T-cell specific proteome, the vast majority of peptides sequenced after elution from MHC were derived from the common proteome. From this pool, we identified several identical peptide epitopes in the T and B cell repertoire derived from common endogenous proteins as well as novel endogenous epitopes with promiscuous binding. These findings indicate that the endogenous HLA-DR-bound peptide repertoire, regardless of APC type and across MHC isotype, is largely derived from the same pool of self-protein.National Institutes of Health (U.S.) (grant P01AI039671)National Institutes of Health (U.S.) (P01AI045757

Obsessive-compulsive disorder in the community : 12-month prevalence, comorbidity and impairment

Although subthreshold conditions are associated with impairment in numerous disorders, research on obsessive-compulsive disorder (OCD) below the diagnostic threshold of DSM-IV in the general population is limited. Estimate the DSM-IV 12-month prevalence, comorbidity and impairment of OCD, subthreshold OCD (i.e., fulfilling some but not all core DSM-IV criteria), and obsessive-compulsive symptoms (OCS) (i.e., endorsement of OCS without fulfilling any core DSM-IV criteria) in a general population sample. Data from the German National Health Interview and Examination Survey - Mental Health Supplement (N = 4181, age 18-65 years), based on the standardized diagnostic interview Munich Composite International Diagnostic Interview. The 12-month prevalence of OCD was 0.7%, subthreshold OCD was 4.5%, and OCS was 8.3%. Subjects in all three groups showed higher comorbidity (odds ratios [ORs] € ≥ 3.3), compared to those without OCS. OCD, subthreshold OCD and OCS were all associated with increased odds of substance abuse/dependence-, mood-, anxiety- and somatoform disorders, with especially strong associations with possible psychotic disorder (ORs € ≥ 4.1) and bipolar disorders (ORs € ≥ 4.7). Participants in all three groups showed higher impairment (ORs € ≥ 3.1) and health-care utilization (ORs € ≥ 2.4), compared to those without OCS, even after controlling for covariates. Individuals with subthreshold OCD and OCS, not currently captured by DSM-IV OCD criteria, nevertheless show substantial comorbidity, impairment and health-care utilization

Examination of the shared genetic basis of anorexia nervosa and obsessive–compulsive disorder

Anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) are often comorbid and likely to share genetic risk factors. Hence, we examine their shared genetic background using a cross-disorder GWAS meta-analysis of 3495 AN cases, 2688 OCD cases, and 18,013 controls. We confirmed a high genetic correlation between AN and OCD (rg = 0.49 ± 0.13, p = 9.07 × 10-7) and a sizable SNP heritability (SNP h2 = 0.21 ± 0.02) for the cross-disorder phenotype. Although no individual loci reached genome-wide significance, the cross-disorder phenotype showed strong positive genetic correlations with other psychiatric phenotypes (e.g., rg = 0.36 with bipolar disorder and 0.34 with neuroticism) and negative genetic correlations with metabolic phenotypes (e.g., rg = -0.25 with body mass index and -0.20 with triglycerides). Follow-up analyses revealed that although AN and OCD overlap heavily in their shared risk with other psychiatric phenotypes, the relationship with metabolic and anthropometric traits is markedly stronger for AN than for OCD. We further tested whether shared genetic risk for AN/OCD was associated with particular tissue or cell-type gene expression patterns and found that the basal ganglia and medium spiny neurons were most enriched for AN-OCD risk, consistent with neurobiological findings for both disorders. Our results confirm and extend genetic epidemiological findings of shared risk between AN and OCD and suggest that larger GWASs are warranted